This proposal is directed towards the development of vaccines for the category B agents Burkholderia pseudomallei and Burkholderia mallei. There is an urgent and acknowledged need to develop better Drophylactic countermeasures through the use of vaccines and immune stimulants for both melioidosis and glanders. We believe it is appropriate to consider these pathogens in parallel in this project because they are closely related at a genetic level, and there is a possibility that common approaches to these diseases can be identified. The aims of this project are to: (1) Identify optimal delivery systems and protein carriers. (2) Develop optimized protein-polysaccharide conjugation methods. (3) Compare efficacy of homologous versus heterologous protein-polysaccharide conjugates. (4) Identify biomarkers and mechanisms of vaccine-mediated protection in acute disease models, including the laboratory mouse, the humanized SCID mouse, and nonhuman primate models. Our principal aim is to devise a non-living vaccine which is able to protect against both 6. pseudomallei and 8. mallei infection. This is an important consideration for eventual licensure and use with potential applications for special populations such as young children, the elderly, pregnant women and immunocompromised subjects. Ultimately, the studies outlined in this proposal will establish a data set to begin the process of a successful submission of an investigative new drug (IND) application to the Food and Drug Administration.